The Association between Infant Colic and the Multi-Omic Composition of Human Milk

Infant colic is a common condition with unclear biologic underpinnings and limited treatment options. We hypothesized that complex molecular networks within human milk (i.e., microbes, micro-ribonucleic acids (miRNAs), cytokines) would contribute to colic risk, while controlling for medical, social, and nutritional variables. This hypothesis was tested in a cohort of 182 breastfed infants, assessed with a modified Infant Colic Scale at 1 month. RNA sequencing was used to interrogate microbial and miRNA features. Luminex assays were used to measure growth factors and cytokines. Milk from mothers of infants with colic (n = 28) displayed higher levels of Staphylococcus (adj. p = 0.038, d = 0.30), miR-224-3p (adj. p = 0.023, d = 0.33), miR-125b-5p (adj. p = 0.028, d = 0.29), let-7a-5p (adj. p = 0.028, d = 0.27), and miR-205-5p (adj. p = 0.029, d = 0.26) compared to milk from non-colic mother-infant dyads (n = 154). Colic symptom severity was directly associated with milk hepatocyte growth factor levels (R = 0.21, p = 0.025). A regression model involving let-7a-5p, miR-29a-3p, and Lactobacillus accurately modeled colic risk (X-2 = 16.7, p = 0.001). Molecular factors within human milk may impact colic risk, and provide support for a dysbiotic/inflammatory model of colic pathophysiology.

Automated summary

Infant colic is a common condition with unclear causes and limited treatment options. This study found that certain molecular factors, such as microbes and micro-ribonucleic acids (miRNAs), in human milk may contribute to colic risk. Higher levels of certain microbes and miRNAs were observed in the milk from mothers of infants with colic, and these factors were associated with colic symptom severity. A regression model involving specific miRNAs accurately predicted the risk of colic. These findings suggest that molecular factors in human milk may play a role in colic and support the dysbiotic/inflammatory model of colic pathophysiology.